Beneficial effect ofCLOCKgene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome

Dec 17, 2013Chronobiology international

How a common CLOCK gene variation and a low-fat diet together relate to insulin metabolism in metabolic syndrome patients

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Abstract

Significant gene-diet interactions were observed for insulin concentrations, HOMA-IR, and QUICKI among 475 MetS subjects based on CLOCK SNP rs1801260.

The study focused on the effects of a low-fat diet versus a Mediterranean diet on metabolic traits in MetS patients.
After 12 months of low-fat intervention, subjects homozygous for the major allele (TT) had lower plasma insulin concentrations and insulin resistance compared to minor allele carriers (TC + CC).
No significant differences in CLOCK genotypes were found in the Mediterranean diet group after the same treatment period.
These findings suggest that the CLOCK gene may influence glucose metabolism in response to dietary patterns in MetS patients.
Personalized dietary adjustments may be necessary for managing MetS due to the complexity of gene-environment interactions.

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Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases. In fact, it has been suggested that the disruption of the circadian system may play a causal role in manifestations of MetS. The aim of this research was to find out whether habitual consumption of a low-fat diet, compared with a Mediterranean diet enriched with olive oil, modulates the associations between common CLOCK single nucleotide polymorphisms (SNPs) (rs1801260, rs3749474 and rs4580704) and lipid and glucose-related traits among MetS patients. Plasma lipid and insulin concentrations, indexes related with insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)) and CLOCK SNPs were determined in 475 MetS subjects participating in the CORDIOPREV clinical trial (NCT00924937). Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% monounsaturated fatty acids (MUFA)) versus low-fat diet (28% fat, 12% MUFA)). We found significant gene-diet interactions between rs1801260 SNP and the dietary pattern for insulin concentrations (p = 0.009), HOMA-IR (p = 0.014) and QUICKI (p = 0.028). Specifically, after 12 months of low-fat intervention, subjects who were homozygous for the major allele (TT) displayed lower plasma insulin concentrations (p = 0.032), lower insulin resistance (HOMA-IR; p = 0.027) and higher insulin sensitivity (QUICKI; p = 0.024) compared with carriers of the minor allele C (TC + CC). In contrast, in the Mediterranean intervention group a different trend was observed although no significant differences were found between CLOCK genotypes after 12 months of treatment. Our data support the notion that a chronic consumption of a healthy diet may play a contributing role in triggering glucose metabolism by interacting with the rs1801260 SNP at CLOCK gene locus in MetS patients. Due to the complex nature of gene-environment interactions, dietary adjustment in subjects with the MetS may require a personalized approach.

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Beneficial effect ofCLOCKgene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome

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